The American Society for Microbiology (ASM) appreciates the opportunity to submit a written statement on the FY 2010 budget for the National Institutes of Health (NIH). The ASM is the largest single life science society with over 42,000 members, many of whom receive funding from the NIH. We are grateful for the $10.4 billion increase in funding for the NIH in the American Recovery and Reinvestment Act (ARRA) and the 3.2 percent increase in funding for NIH in the FY 2009 Appropriations Act. The additional ARRA funding enables NIH to support the ARRA goals to create and save jobs and increase purchasing power, as well as advance scientific research. The nation’s biomedical research enterprise will be kept more robust at a time when it is experiencing the adverse effects of the economic downturn and years of flat funding.
As Congress considers the FY 2010 appropriation for NIH, the ASM recommends a budget of $32.4 billion, a 7 percent increase. The recommended funding increase will help NIH keep pace with expanded research opportunities and higher costs. It is important for NIH to prepare for the post-stimulus years, in 2011 and beyond. It is also important to resume sustainable NIH funding, avoiding fluctuations for research and training programs that can disrupt projects, training, careers and research progress. To perpetuate the benefits of ARRA funding, it is vitally important to provide sustained growth for the NIH in FY 2010 and beyond.
Over 83 percent of the NIH budget is awarded through 50,000 competitive grants awarded to more than 325,000 researchers at over 3,000 universities, medical schools, and other institutions in all 50 states. About 10 percent of the NIH budget supports research in NIH laboratories conducted by nearly 6,000 scientists. Research project grants are highly productive in terms of medical advances to benefit public health. NIH funding contributes to the nation’s economic recovery by stimulating new opportunities and investments in biotechnology and related industries, as well as expanding the skilled workforce critical to US competitiveness in science and technology. NIH funding also impacts allied health workers, technicians, students, trade workers and others who receive the leveraged benefits from NIH funding.
The following describes some of the compelling reasons for increased and sustained support for the NIH research mission and its proven benefit to technological innovation and public health.
NIH Research is Critical to Scientific Progress
NIH institutes and centers fund research programs that address the nation’s challenges of safeguarding public health, security, and the economy. The National Institute of Allergy and Infectious Diseases (NIAID), for example, focuses on research to understand, treat, and prevent infectious, immunologic, and allergic diseases, leading to the development of vaccines, therapies and diagnostic tools. The NIAID also funds research on medical countermeasures against potential bioterror agents. The National Institute of General Medical Sciences (NIGMS) supports basic research on life processes in fields such as computational biology, genetics, and bioinformatics. NIH resources invested in the agency-wide Roadmap initiatives make possible projects that hold great potential but might otherwise not be funded due to difficulty and scope. Recently funded Roadmap projects include a network of nine centers using high-tech screening methods for drug discovery.
The NIH funding to individual researchers and research groups, through competitive peer-reviewed grants, is of particular consequence to the US research enterprise. More than 120 discoveries made by NIH and NIH-supported researchers have garnered Nobel Prizes, and NIGMS has funded the Nobel Prize-winning work of 64 scientists. More than three-fourths of the US recipients of the Nobel Prize in Physiology or Medicine received NIH support prior to their award. In FY 2009 NIH is striving to lower the average age of first-time grant recipients to refresh the nation’s scientific investigator pool and help revitalize research in the United States. Our national anxiety over waning global competitiveness and a shrinking technical workforce argues for sustained NIH funding for both new and established investigators.
NIH investigator initiated grants create new opportunities for original biomedical inquiry and expand training environments for students in technical fields. Investigator-initiated research projects lead to inventive solutions for medical problems. Each year, NIH also identifies, in consultation with the extramural research community, targeted areas within an emerging need or opportunity, and then requests grant applications from US researchers. Focused opportunities announced last year by NIAID include studies to advance vaccine safety and development of assays for high-throughput drug screening. NIGMS-featured areas currently include computational models to detect, control and prevent emerging infectious diseases. NIGMS also awards grants for nontraditional research through its Exceptional, Unconventional Research Enabling Knowledge Acceleration (EUREKA) program. NIH has placed new emphasis on supporting high-impact transformative research that might create new disciplines, revolutionary technologies, or otherwise radically change biomedical research. In 2008, it initiated transformative grant funding to foster investigator-initiated work considered high-risk but exceptionally promising.
NIH Research Yields Medical Advances
NIH supported research consistently produces significant discoveries with both real-world relevance and potential future use against emerging health threats. The following are selected examples of recently reported research that illustrate the vitality and creativity supported by NIH funding.
Antimicrobial Resistance and Drug Discovery. Drug resistance spreading among microbial pathogens is complicating control of infectious diseases and adding to rising health care costs. Response by US research institutions has been aggressive, including creation of a Federal Interagency Task Force co-chaired by NIAID, the Centers for Disease Control and Prevention, and the Food and Drug Administration. Causes of drug resistance are many, from overuse of prescription drugs to natural microbial mutations, and NIAID’s research portfolio is equally diverse. In FY 2007, the Institute invested more than $800 million to support basic and translational research on antimicrobials and on drug resistance. Recent results include:
Scientists from NIAID, California, and China studied the genetics of the major strain of methicillin-resistant Staphylococcus aureus (MRSA), concluding that a radical shift may be needed in how scientists design MRSA therapeutics. MRSA causes an estimated 94,000 cases of infection annually in the United States, with over 19,000 deaths.
NIGMS-funded researchers are developing a new generation of antibiotic compounds that do not elicit drug resistance. The enzyme-inhibitor compounds interfere with "quorum sensing” —a process by which bacteria communicate with each other. Those in the current study work against Vibrio cholerae, which causes cholera, and E. coli 0157:H7, the food contaminant that annually causes about 110,000 illnesses in the United States.
To circumvent antimicrobial resistance, NIH researchers and their extramural collaborators are intensifying research strategies better suited to rapidly changing pathogens and disease demographics. These include state-of-the-art technologies that fuel 21st century drug discovery. A recent example is NIGMS-funded research using mass spectrometry technology to determine the molecular structure of a class of natural compounds called nonribosomal peptides (NRPs), intensely studied for their drug potential (penicillin is an NRP). A significant advance over previous approaches, it may help reprogram nonpathogenic E. coli into NRP minifactories.
Infectious Diseases. Infectious diseases remain among the most difficult global health challenges, accounting for about one-quarter of all deaths and nearly two-thirds in sub-Saharan Africa. At NIAID and NIGMS, multiple programs and interdisciplinary strategies target the major causes of global death and disability, with cutting-edge tools like genomics and nanotechnology.
Influenza Despite the availability of influenza drugs and vaccines, seasonal influenza still kills more than 250,000 people worldwide each year. Public health officials are now concerned about reports that 98 percent of a H1N1 influenza virus strain (one of three circulating in the 2008-2009 season) are resistant to oseltamivir (Tamiflu), the leading influenza drug, compared to 11 percent resistance among all viral strains during the 2007-2008 season. The possibility of an influenza pandemic caused by the more lethal H5N1 avian flu virus has mobilized an international response from health agencies and medical researchers. In January, the Department of Health and Human Services awarded a contract to build the first US manufacturing facility for cell-based influenza vaccines, expected to increase the nation’s current capacity to make vaccine by at least 25 percent and much less time. NIH funding contributed to this major advance in vaccine production and to other recent advances, such as:
NIAID-supported scientists used new monoclonal techniques to create human influenza-fighting antibodies in the laboratory in a matter of weeks, rather than the months previously required. The antibodies have potential for diagnosis and treatment regimens that can respond more quickly to newly emerging strains of influenza.
NIGMS-funded researchers used super-computer capabilities to identify more than two dozen new candidate drugs to treat avian influenza (“bird flu”), in preparation for a possible pandemic of drug-resistant H5N1 virus strains.
Three research teams and a computer informatics group¯part of the NIGMS-funded Models of Infectious Disease Agent Study (MIDAS) Network¯modeled pandemic influenza in the United States, concluding mitigation is possible with prompt, coordinated use of social-distancing measures and antiviral treatment until vaccine is available.
HIV/AIDS An estimated 33 million adults and children are living with HIV infection worldwide, and about 2 million die each year from related causes. In the United States, where nearly 546,000 people have died thus far from HIV/AIDS-related illnesses, there currently are an estimated 1.1 million infected, with 21 percent unaware of their infection. HIV/AIDS as both a domestic and global threat is a high priority at NIH. Difficulties in developing preventative vaccines prompted a 2008 NIH vaccine summit and subsequent reexamination of NIH’s research agenda. NIH-supported basic research is steadily adding to our understanding of HIV/AIDS, evidenced by recent discoveries in mechanisms of HIV protease inhibition and the NIGMS-funded success in seeing microscopically for the first time molecules grouping in living cells to form single HIV particles. Other recent advances include:
A vaginal gel to prevent HIV infection in women has shown encouraging signs of success in a clinical trial in Africa and the United States. This is the first human clinical study to suggest that a microbicide may prevent male-to-female sexual HIV transmission.
An extended course of the antiretroviral drug nevirapine helps the breastfeeding babies of HIV-infected mothers remain HIV-negative and live longer, according to several new studies. About 150,000 infants worldwide acquire HIV annually through breastfeeding.
The incidence of childhood illness and death due to HIV infection can be dramatically decreased by testing very young babies for HIV and giving antiretroviral therapy (ART) immediately to those found infected¯giving ART to HIV-infected infants beginning at an average age of 7 weeks made them four times less likely to die in the next 48 weeks.
Tuberculosis One-third of the world’s 6.7 billion people are thought to be infected by Mycobacterium tuberculosis (Mtb), the microbe that causes tuberculosis. An estimated 13.7 million have the active form. Each year, about 1.7 million die from this age-old disease that has adopted some disturbing modern-day features, striking as co-infections with the HIV virus and becoming resistant to drug therapies used to treat tuberculosis. In 2007, about 9.3 million people developed new cases of TB; 1.37 million were also HIV positive. The rapid spread of multidrug- and extensively drug-resistant forms (MDR TB/XDR TB) is alarming¯MDR TB currently accounts for an estimated 5 percent of all TB cases and the frequently fatal XDR TB has been detected in 46 countries thus far. In April 2008, NIAID launched an aggressive research agenda against drug-resistant tuberculosis. NIH-supported research from the past year includes:
NIAID scientists and industry collaborators found that, when the candidate TB drug PA-854 is metabolized inside Mtb bacteria, a lethal dose of nitric oxide gas is produced, killing the pathogen and suggesting new ways to develop drugs capable of killing latent TB bacteria. Currently there are no drugs available to target latent tuberculosis infections.
Scientists reported that two FDA-approved drugs work in tandem to kill the tuberculosis pathogen and could help counter drug-resistant forms. The drugs are already used to treat other bacterial diseases, but their effectiveness against TB bacteria had not been studied. NIAID is planning a clinical trial this year in patients with MDR TB and XDR TB.
Malaria Nearly half of the world’s population is at risk of contracting malaria, a preventable and curable mosquito-borne disease in more than 100 countries. The World Health Organization (WHO) estimates that 300 to 500 million cases of clinical malaria worldwide occur each year, killing 1.3 million people. Unfortunately, its impact is intensifying with the emergence of drug-resistant parasites and insecticide-resistant mosquitoes. In April 2008, NIAID announced its new strategic plan to accelerate malaria control and eradication. NIH research often involves international partners and encompasses all aspects of malaria, including these recent examples:
NIGMS funding supported the genetic decoding of the parasite responsible for 40 percent of infections, Plasmodium vivax, one of four malaria parasites that routinely affect humans.The most common species outside Africa (including the United States), P. vivax is increasingly resistant to some antimalarial drugs.
The NIAID-funded Malaria Research and Training Center in Mali completed the first clinical trial of a vaccine to block the malaria parasite from entering human blood cells.
NIGMS-supported research described how harmless E. coli bacteria can be harnessed to synthesize an antimalarial compound in bulk, far less expensive than the current process.
Infectious Disease Research Uses Interdisciplinary Strategies and New Technologies
NIAID and NIGMS, like other NIH institutes and centers, support productive basic research on literally hundreds of diseases, from periodic foodborne E. coli or Salmonella outbreaks to isolated cases of Ebola fever or anthrax. This enormous responsibility forces constant adaptation to new challenges, often through greater reliance on interdisciplinary strategies or novel research tools and technologies¯epitomized by the large-scale genetics-based initiatives made possible with today’s powerful computing capabilities. In 2008, NIH launched a multi-Institute epigenomics initiative to better understand the role of the environment in regulating mammalian genes, through genome mapping, data analysis, and technology development. NIH also agreed to share databases from its Human Microbiome Project in support of the newly formed International Human Microbiome Consortium. Characterizing the human microbiome, which is the collective DNA of all the microbes living in or on the human body, will elucidate the relationship between microbes and humans during health and disease. Shared sample repositories overseen by databases expedite information exchange among scientists. Computerized screening of pathogen genomes similarly accelerates the search for treatments, vaccines, and diagnostics.
The ASM is thankful that Congress recognizes both the medical benefits and economic impacts of biomedical research and has provided an infusion of funding for the NIH to uncover new knowledge that will improve public health. Investing in NIH will impact the health of people for years to come and the biomedical community is working to ensure wise investment of the new resources in FY 2009. We are confident that investments in the NIH will result in new discoveries and innovations that can address many of our health and economic challenges.